The molecular mechanisms regulating oncogenic signalling by sphingosine kinase 1 phosphorylation and localisation

鞘氨醇激酶是一种产生脂质信号分子鞘氨醇磷酸的酶，其参与多种重要哺乳动物细胞功能的调节。研究发现，鞘氨醇激酶参与增强细胞的生长和存活。鞘氨醇激酶的失调与肿瘤发生有关，如果其活性可以被阻断，肿瘤的大小可以减小。因此，这为癌症的治疗干预提供了潜在的靶点。然而，细胞调节鞘氨醇激酶的方式并不清楚。已知鞘氨醇激酶的磷酸化增加该酶的活性，并且还引起其在质膜上的定位的移动。我们已经发现，这两个过程是必不可少的鞘氨醇激酶的致瘤作用，但很少有人知道这些过程是如何在细胞中实现的。本研究将探讨这一问题，认为了解这些过程将有助于开发新的药物来阻断鞘氨醇激酶的致瘤作用。

Sphingosine kinase is an enzyme that produces the lipid signalling molecule, sphingosine phosphate that is involved in the regulation of a diverse array of important mammalian cellular functions. Studies have found that sphingosine kinase is involved in enhancing the growth and survival of cells. Disregulation of sphingosine kinase is involved in tumorigenesis, and if its activity can be blocked, tumor size can be reduced. Therefore, this provides a potential target for therapeutic intervention in cancer. However, the manner by which cells regulate sphingosine kinase is not well known. It is known that phosphorylation of sphingosine kinase increases the activity of this enzyme, and also causes a shift in its localisation the the plasma membrane. We have found that both of these processes are essential for the tumorigenic effects of sphingosine kinase, but very little is known about how these processes are achieved in the cell. This study will investigate this problem with the view that understanding these processes will assist in the development of new drugs to block the tumorigenic effects of sphingosine kinase.